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Characterization of Two Cell Lines with Distinct Phenotypes Established from a Patient with Small Cell Lung Cancer¹

Department of Internal Medicine, Division of Hematology-Oncology [G. B., G. J., K. H.], Philipps-University Marburg, 3550 Marburg, Federal Republic of Germany; Department of Human Genetics [A. K.], Liebig-University Giessen, 6300 Giessen, Federal Republic of Germany; and National Cancer Institute-Navy Medical Oncology Branch, National Cancer Institute and National Naval Medical Center [B. E. J., A. F. G.], Bethesda, Maryland 20814

Two small cell lung cancer (SCLC) cell lines were established from pericardial and pleural effusions of a patient with histopathologically proven SCLC of the oat cell type. Chemotherapy was administered without response during the 148-day period prior to the establishment of the first cell line, SCLC-22H, and some of the same drugs were administered in the 15 days prior to the establishment of the second cell line, SCLC-21H. Both cell lines differed markedly in their biochemical, kinetic, and morphological properties. Although the biomarkers L-Dopa decarboxylase, bombesin, carcinoembryonic antigen, and neurotensin were detectable in SCLC-22H, they were undetectable or low in SCLC-21H. The population doubling time was twice as fast and the colony forming efficiency higher in SCLC-21H than in SCLC-22H. They both expressed high concentrations of the SCLC marker enzymes neuronspecific enolase and the creatine kinase isoenzyme BB and showed no significant differences in their chromosomal characteristics. c-myc was amplified and expressed in both cell lines, and SCLC-21H had an additional rearranged and amplified EcoRI c-myc fragment. Morphological differences were apparent in liquid culture, cytology, and xenograft histology; SCLC-21H grew much more loosely than SCLC-22H, and had more prominent nucleoli and more abundant cytoplasm. Ultrastructurally dense core granules were present in both cell lines. SCLC-21H thus expressed properties of the variant cell type of SCLC, whereas SCLC-22H had mixed classic/variant features. An in vivo progression of the patient's tumor from a pure small cell to a mixed small cell/large cell morphology could be demonstrated, which suggests that cell line SCLC-22H represents a cell type characteristic for the transitional phase of the tumor. The features of this cell line therefore define a new subclass of SCLC called transitional cell type. SCLC-22H may be of use to study the mechanisms involved in the classic to variant transition, which probably has a considerable impact on the prognosis and response to therapy.

¹ This work was supported by the SFB 215 of the German Research Society.

² To whom requests for reprints should be addressed, at Klinikum der Philipps-Universitaet, Zentrum fuer Innere Medizin, Abteilung Haematologie/Onkologie, Baldingerstrasse, 3550 Marburg, Federal Republic of Germany.

Received 1/ 4/86. Revised 9/26/86. Revised 12/31/86. Accepted 1/ 7/87.